Theoretical studies on sulfanilamide and derivatives with antibacterial activity: conformational and electronic analysis

Abstract

Quantum chemical methods have been used to study the conformational and electronic properties of sulfanilamide and derivatives with antibacterial activity. Calculations at B3LYP/6-311++G(3df,2p) level of theory predict the existence of four conformers for sulfanilamide depending on the orientation of p-amino and amide groups. Focusing on the sulfonamide moiety, amide NH(2) and SO(2) groups could exist either in an eclipsed or staggered arrangement. Gas-phase results predict the eclipsed conformer to be most stable but opposite to what has been rationalized previously, no stabilizing hydrogen bonds between those groups has been found through NBO analysis. When solvent effect is taken into account through the IEF-PCM method, staggered conformer is preferred; in fact, eclipsed conformation changed when explicit solvent molecules were included. Conformational analysis of all derivatives has shown two global minima which are specular images. Five out of the seven derivatives studied adopted a particular minimum energy conformation with very similar geometries.

N-(2-Amino-5-chlorophenyl)-2-bromobenzenesulfonamide

“…They found applications as HIV inhibitors (Lu & Tucker, 2007), antimicrobial drugs (Tappe et al, 2008), carbonic anhydrase inhibitors (Chegwidden et al, 2000), anti-tumor agents (Purushottamachar et al, 2008), just to name a few. In this respect a lot of publications have appeared reporting structural data of compounds containing the sulfonamide function (Parkin et al, 2008, Altamura et al, 2009, Perlovich et al, 2009, Perlovich et al, 2011,Vega-Hissi et al, 2011, Altamura et al, 2012. The molecule, as expected, has a staggered conformation about the N-S bond, with the N lone pair bisecting the OŜO angle (Table 1, Fig.…”

N,N-Diethyl-2-(4-methylbenzenesulfonamido)benzamide

“…Because the structural and conformational properties of a compound usually are related to its biological properties, their study would provide useful information to design new effective drugs. In this regard, there are many recent publications reporting structural data on related sulfonamides (Parkin et al, 2008, Altamura et al, 2009, Perlovich et al, 2009, Perlovich et al, 2011,Vega-Hissi et al, 2011.…”

“…For the biological activity of compounds having the sulfonamide -SO 2 NH-group, see: Lu & Tucker (2007); Tappe et al (2008); Chegwidden et al (2000); Purushottamachar et al (2008). For structural and conformational studies of molecules featuring the sulfonamide moiety, see: Parkin et al (2008); Perlovich et al (2009Perlovich et al ( , 2011; Altamura et al (2009); Vega-Hissi et al (2011). Table 1 Hydrogen-bond geometry (Å , ).…”

Activating interactions of sulfanilamides with T cell receptors

“…angle with the N to S-C bond in the SA core, which has a range 110.0˚ +/− 2.5 in either direction, was the primary cause [28,29].…”